The objective of this research is to investigate the membrane mechanisms that underlie abnormal, prolonged, repetitive discharge of impulses, and abnormal contractions of skeletal muscle fibers. Electrophysiological and pharmacological methods will be used to continue my study of the skeletal muscle of normal and congenitally myotonic goats and to compare the repetitive responses and other myotonic signs in the muscle of various species when these conditions are induced by chemical agents, denervation, ionic changes, hereditary disease, and other treatments. The voltage clamp method will be introduced to this project with the intention of better defining the ionic basis of myotonic behavior of these fibers. Special attention will be paid to the generality of the low chloride conductance hypothesis, the mechanism of accommodation in muscle, possible involvement of the end plate and excitation-contraction coupling in myotonia, the nature of the chloride conductance channel, and role of the transverse tubular system in the myotonic response. The ultimate aims are to elucidate mechanisms of repetitive responsiveness and other signs as they occur in myotonia congenita or elsewhere, and to relate this knowledge to excitation of normal membrane, and the action of drugs or disease processes which alter these properties, thus making possible the control of these phenomena.